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Undergraduate Research Project Management System

What Role Does Serine 122 of Histone H2A Serve in DNA Damage Repair Pathways?

Status Current
Seeking Researchers No
Start Date 07/01/2009
End Date 06/30/2010
Funding Source Alaska Heart Institute Fellowship
Funding Amount
Community Partner
Related Course
Last Updated 07/13/2009 11:14PM
Keywords DNA

People

Faculty
  Jocelyn Krebs

Student Researchers
  Shira Wolfe

Abstract

Living cells are continuously bombarded by environmental stressors and mutagens. DNA is particularly susceptible to damage from sources such as UV light, ionizing radiation, chemical mutagens, and reactive oxygen species. Fortunately, DNA repair mechanisms are in place to minimize genetic instability that could ultimately cause disease or cell death. In eukaryotes, nuclear DNA is highly organized into chromatin, consisting of repeating units called nucleosomes. Nucleosomes consist of 147 bp of DNA wrapped around a core histone octamer (2 each of H2A, H2B, H3, H4). Previous research in the Krebs Laboratory has demonstrated that a number of amino acid residues of the H2A tails play a role in different DNA repair pathways, however, serine 122 on histone H2A is the only residue found to be critical for the reapir of all types of DNA damage studied thus far. When this residue is mutated to an alanine (now referred to as S122A), preventing the addition of covalent modifications, the cells are extremely sensitive to all types of DNA damage. While it is clear that S122 is important in repair, the mechanism in which S122 assists in DNA repair has not been resolved. By deleting genes known for their roles in different repair pathways, and combining those deletions with the S122A mutation, I intend to determine the involvement of S122 in specific pathways. This work will provide the information needed to begin finding direct interactions of S122 within repair networks.

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